Search PubMed⌕ Search

Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 685 records · Page 38Linked to original sources
PubMed1994

Intravenous immune globulin in chronic lymphocytic leukaemia.

The most common complication of chronic lymphocytic leukaemia (CLL) is infection, which occurs mainly in advanced stages of disease or in those patients with hypogammaglobulinaemia. Intravenous immune globulin (IVIG) has been shown to be a useful prophylactic therapy against infections in such patients. A randomized, double-blind study on 36 patients receiving either 500 mg/kg or 250 mg/kg IVIG every 4 weeks was undertaken to determine the dose regimen required. There was no significant difference in the two treatment groups and we found that CLL patients were equally protected with low-dose IVIG.

Agammaglobulinemia↗
PubMed1994

The use of intravenous immune globulin in multiple myeloma.

Patients with multiple myeloma suffer from serious bacterial infections throughout the course of the disease. This is probably associated with reduced polyclonal immunoglobulin synthesis. Prophylactic intravenous immune globulin (IVIG) reduces the incidence and recurrence of these infections in the stable phase of the disease. Infections at times of induction chemotherapy and/or relapse have a wider range of causative organisms. Such susceptibility may be associated with abnormal phagocytic function following chemotherapy.

Bacterial Infections↗
PubMed1994

Vasectomy and prostate cancer risk in China.

Vasectomy has been reported to be associated with an increased risk of prostate cancer in western countries. A hospital-based case-control study was conducted in 12 cities in China to evaluate the relationship between vasectomy and prostate cancer risk in China, a low-risk country with rising incidence and increasing use of vasectomy. Interviews were conducted with 138 histologically confirmed prostate cancer cases diagnosed during 1989-1992 and 638 controls (158 hospital cancer, 158 hospital noncancer, and 322 neighborhood controls) of similar ages. Vasectomy at least 10 years prior to interview was reported by 10% of the cases versus 3% of the controls. Odds ratios for prostate cancer associated with vasectomy were 2.0 (95% confidence interval, 0.7-6.1), 3.3 (95% confidence interval, 1.0-11.3), and 6.7 (95% confidence interval, 2.1-21.6), respectively, when hospital cancer, hospital noncancer, and neighborhood controls were used for comparison. Although detection bias is of concern, the data suggest that in China, men with a history of vasectomy may experience an increased risk of prostate cancer.

Aged↗
PubMed1994

CT-diagnosis of deep-seated lipomas with alarming symptoms.

Deep-seated lipomas can present with symptoms very different from those of the common subcutaneous variety. Rapid growth and nerve encroachment may cause suspicion of malignancy. The case histories as well as the clinical and radiographic findings of 2 patients with alarming symptoms from deep-seated lipomas of hand and forearm, respectively, are described. By means of CT an accurate preoperative diagnosis could be made, and surgery planned accordingly.

Adult↗
PubMed1993

Turnover of fluorescent nucleoside triphosphates by isolated immobilized myosin filaments. Transient kinetics on the zeptomole scale.

Recent developments of in vitro motility assays have allowed the sliding velocity and force generation to be measured when a single actin filament interacts with a small number of immobilized myosin molecules. In contrast, the associated ATPase activities have been estimated from the whole population of molecules in the flow cell using steady-state kinetics. For a more unambiguous estimate of the crossbridge step size, it would be desirable to measure the ATPase activity of those molecules actually under observation in the in vitro assay in real time. As a start to solving this formidable problem we have investigated the use of fluorescent ATP analogues as probes to measure the ATPase activity of immobilized myosin filaments. Turnover rates for the substrate analogue, FEDA-ATP (an analogue in which a fluorescein moiety is linked via an ethylenediamine chain to the ribose of ATP) were recorded by displacement of the steady-state intermediate with excess ATP. Using epifluorescence light microscopy, small clumps of rabbit skeletal and scallop striated muscle synthetic thick filaments and single native clam (Mercenaria) red adductor muscle thick filaments were assayed. The latter filaments contain several thousand myosin molecules and thus they represent the application of transient kinetic methodology on the zeptomole scale. In the presence of Ca2+, the derived rate constants for FEDA-ATP turnover are close to those expected for the same preparations in solution (0.06 s-1 for rabbit skeletal, 0.2 s-1 for scallop and clam adductor muscle myosins), indicating that immobilization does not have a significant effect on the ATPase activity. In the absence of Ca2+, molluscan preparations show a slower FEDA-ATP turnover rate but they do not appear as well regulated as in solution. In such microscope assays the observed displacement rate does not reflect the true turnover rate owing to photobleaching, and possibly regulatory light chain depletion. Future developments for extending this assay to the actin-activated state are discussed.

Actin Cytoskeleton↗
PubMed1993

Non-synaptic modulation of dorsal column conduction by endogenous GABA in neonatal rat spinal cord.

GABAA receptor activation can modulate axonal conduction in the isolated dorsal column of the neonatal rat spinal cord in vitro. However, it is not known whether axonal conduction in the dorsal column can be modulated by endogenous GABA in the developing spinal cord. We consequently compared the effects of GABA, a GABAA agonist, and a GABA uptake inhibitor on axonal conduction in the dorsal column of hemisected neonatal (0- to 9-day-old) rat spinal cords in vitro. Extracellular compound action potentials evoked by supramaximal stimuli were recorded at two points with glass microelectrodes. GABA (10(-4) to 10(-3) M) reversibly decreased the compound action potential amplitude and the population conduction velocity. At 10(-4) M, compound action potential amplitudes fell by 45.0 +/- 6.5% of control while the conduction velocity slowed by 11.8 +/- 4.3% (n = 5). The GABAA receptor agonist, isoguvacine, mimicked the effects of GABA on the dorsal column compound action potential. In contrast, while GABA at 10(-5) M decreased the amplitude by 7.7 +/- 3.1%, it increased conduction velocity by 9.7 +/- 1.3% (n = 5). The GABA uptake inhibitor, nipecotic acid (10(-3) M), consistently decreased the compound action potential amplitude by 17.7 +/- 6.5% (n = 6) but the conduction velocity slowed in four out of six preparations. In two instances, nipecotic acid decreased the amplitude and increased the conduction velocity. The effects of nipecotic acid on the dorsal column compound action potential were blocked in the presence of the GABAA antagonist bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Analysis of a cloned Francisella tularensis outer membrane protein gene and expression in attenuated Salmonella typhimurium.

We have determined the nucleotide sequence of fopA from Francisella tularensis. Using the polymerase chain reaction fopA was detected in high and low virulence biotypes of F. tularensis. fopA was stably maintained in pBluescript in attenuated Salmonella typhimurium where FopA was expressed and located in the outer membrane. This recombinant will be suitable for studies on the role of FopA in immunity against tularaemia.

Amino Acid Sequence↗
PubMed1993

Prognostic significance from 10-year follow-up of a qualitatively normal planar exercise thallium test in suspected coronary artery disease.

A normal exercise thallium-201 scintigram has been shown to confer an excellent prognosis over a 1- to 4-year follow-up period. However, progression of coronary disease could result in cardiovascular mortality with increasing time. Therefore, the vital status of 309 patients with normal stress thallium myocardial imaging was determined after an average of 10.3 years. Deaths were classified as cardiac or noncardiac. Statistical analysis was performed using Kaplan-Meier survival curves. Standardized mortality ratios were calculated and compared with those of an age- and sex-matched general population. Follow-up was complete in 288 patients (93%). Of 18 deaths, only 3 were cardiac; the remaining 15 were mainly secondary to cancer. Thus, cardiac mortality was 1% and total mortality 6.3% at 10 years. In addition, both all-cause and cardiac mortality rates were significantly less than would be expected in an age- and sex-adjusted segment of the general population. Thus, normal exercise thallium scintigraphy retains its high negative predictive value for death < or = 10 years after initial testing. This supports the use of stress thallium imaging to predict which patients with suspected coronary artery disease are at low risk for cardiac death and thus do not need invasive testing.

Coronary Angiography↗
PubMed1993

GC base sequence recognition by oligo(imidazolecarboxamide) and C-terminus-modified analogues of distamycin deduced from circular dichroism, proton nuclear magnetic resonance, and methidiumpropylethylenediaminetetraacetate-iron(II) footprinting studies.

The DNA binding properties of a series of imidazole-containing and C-terminus-modified analogues 4-7 of distamycin are described. These analogues contain one to four imidazole units, respectively. Data from the ethidium displacement assay showed that these compounds bind in the minor groove of DNA, with the relative order of binding constants of 6 (Im3) > 7 (Im4) > 5 (Im2) > 4 (Im1). The reduced binding constants of these compounds for poly(dA-dT) relative to distamycin, while they still interact strongly with poly(dG-dC), provided evidence of GC sequence acceptance. The preferences for GC-rich sequences by these compounds were established from a combination of circular dichroism (CD) titration, proton nuclear magnetic resonance (1H-NMR), and methidiumpropylethylenediaminetetraacetate-iron(II) [MPE.Fe-(II)] footprinting studies. In the CD studies, these compounds produced significantly larger DNA-induced ligand bands with poly(dG-dC) than poly(dA-dT) at comparable ligand concentrations. 1H-NMR studies of the binding of 5 to d-[CATGGCCATG]2 provided further evidence of the recognition of GC sequences by these compounds, and suggested that the ligand was located on the underlined sequence in the minor groove with the C-terminus oriented over the T residue. MPE footprinting studies on a GC-rich BamHI/SalI fragment of pBR322 provided unambiguous evidence for the GC sequence selectivity for some of these compounds. Compounds 4 and 7 produced poor footprints on the gels; however, analogues 5 and 6 gave strong footprints.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

In vitro cytotoxicity of GC sequence directed alkylating agents related to distamycin.

Imidazole containing analogues 7, 10, and 17 of distamycin wherein the C-terminus contain a dimethylamino moiety have been shown to selectively bind to the minor groove of GC-rich sequences. Accordingly, these agents were employed as vectors for the delivery of a variety of alkylating agents to GC-rich sequences. The alkylating agents are attached to the N-terminus of these vectors thus providing the benzoyl N-mustards (8, 15, and 18 that contain one, two, and three imidazole units, respectively) and substituted acetamides 11-14. Results from the ethidium displacement assay for the formamides 7, 10, and 17 and mustards 15 and 18 showed that these agents bind to calf thymus DNA, poly(dA.dT), poly(dG.dC), and also to coliphage T4 DNA, thus confirming their binding in the minor groove. The reduced binding constants of these compounds for poly(dA.dT) while still binding as strongly, or more strongly, to poly(dG.dC) than distamycin provided evidence for their acceptance of GC sequences. Selectivity for GC-rich sequences was also indicated by CD titration studies. Titration of 10, 15, 17, and 18 to poly(dA.dT) produced weak drug-induced CD bands at approximately 330 nm; however, interaction of these agents to poly(dG.dC) in equimolar drug concentrations gave strong bands in this region. Results from dialysis and cross-link gel experiments provided evidence of alkylation and cross-linking of DNA by the mustards which could explain their enhanced cytotoxicity over the formamido analogues. The bifunctional N-mustard-containing analogues 15 and 18 are significantly more cytotoxic than the monoalkylating acetamides 11-14. The mustards also exhibited significant activity against cell lines derived from solid tumors such as melanomas, ovarian cancers, CNS cancers, and small cell lung cancer.

Alkylating Agents↗
PubMed1993

Pharmacologic effects of cisplatin microspheres on peritoneal carcinomatosis in rodents.

BACKGROUND: A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), has been developed in dosage form for peritoneal carcinomatosis and has been designed to release 70% of the incorporated cisplatin slowly during a period of 3 weeks. In this study, its pharmacologic effects were examined in rodents. METHODS: CDDP-MS was tested to determine (1) tissue distribution of cisplatin after intraperitoneal administration of cisplatin at 3.0 mg/kg body weight to rats, (2) acute toxicity in mice when injected intraperitoneally, and (3) therapeutic effects on peritoneal carcinomatosis induced by transplantable M5076 tumors in mice. RESULTS: These experiments revealed the following: (1) CDDP-MS resulted in a higher cisplatin concentration in tissues adjacent to the peritoneum for a longer period, and the concentration of cisplatin measured in the rest of the body was lower than that delivered by the cisplatin aqueous solution; (2) the 50% lethal dose value, determined by the Litchfield-Wilcoxon method, was 23.8 mg/kg body weight in CDDP-MS in terms of cisplatin, whereas in the cisplatin aqueous solution it was 13.5 mg/kg body weight; (3) CDDP-MS enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin aqueous solution. CONCLUSIONS: Intraperitoneal CDDP-MS releases cisplatin into the peritoneal cavity for a long time, and it results in less systemic toxicity and greater therapeutic effects on peritoneal carcinomatosis than does cisplatin aqueous solution.

Animals↗